The overall objectives of this research are: (1) to characterize possible changes in myogenic tone and calcium permeability in vascular smooth muscle (VSM) of hypertensive animals; (2) to determine the role of phosphoinositides in VSM membrane permeability to Ca ions; (3) to determine whether VSM phosphoinositide metabolism is altered in hypertension and attempt to relate these alterations to possible changes in Ca ions permeability. The major thrust of the research during the first year has been aimed at resolving the following paradox: Why is isolated VSM from hypertensive animals hyporesponsive to various contractile agonists, whereas in vivo and in perfused vascular systems there is always hyper-responsiveness to these agents? In order to answer this question, we have first of all confirmed the observation of Noon, et al. (Proc. Natl Acad. Sci. 75:1605, 1978) that VSM from SHR exhibits a decrease in "resting" tension upon exposure to Ca ions-free solution. Strips of aortic SM were also shown to be hyporesponsive in Ca ions-containing medium but not when first exposed to Ca ions-free solution, then to Ca ions plus agonist. In another type of experiment it was shown that induction of tone in normotensive aorta by the use of 15 mM KCl produced a tissue which responded like SHR VSM in that it relaxed upon exposure to Ca ions-free solution and showed apparent hyporesponsiveness to norepinephrine. It thus appears that decreased responsiveness of SHR VSM is only an apparent hyporesponsiveness which is due to inherent myogenic tone.